HEM iSMART-D: Trametinib + Dexamethasone + Chemotherapy in Children With Relapsed or Refractory Hematological Malignancies

Sponsor
Princess Maxima Center for Pediatric Oncology
Study ID
NCT05658640
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Acute Lymphoblastic Leukemia, in Relapse
  • Lymphoblastic Lymphoma (Precursor B-Lymphoblastic Lymphoma/Leukaemia) Recurrent
  • Lymphoblastic Lymphoma (Precursor B-Lymphoblastic Lymphoma/Leukaemia) Refractory
  • Lymphoblastic Lymphoma (Precursor T-Lymphoblastic Lymphoma/Leukaemia) Recurrent
  • Lymphoblastic Lymphoma (Precursor T-Lymphoblastic Lymphoma/Leukaemia) Refractory

Eligibility Criteria

Sex
ALL
Age
1 Year - 21 Years
Healthy Volunteers
Not accepted

Interventions

  • Trametinib — DRUG
    Oral
  • Dexamethasone — DRUG
    Oral/ Intravenous
  • Cyclophosphamide — DRUG
    Intravenous
  • Cytarabine — DRUG
    Intravenous
  • Intrathecal chemotherapy — DRUG
    IT: Methotrexate +/- prednisone/hydrocortisone/cytarabine according to the degree of central nervous involvement

Study Details

HEM-iSMART is a master protocol which investigates multiple investigational medicinal products in children, adolescents and young adults (AYA) with relapsed/refractory (R/R) ALL and LBL. Sub-protocol D is a phase I/II trial evaluating the safety and efficacy of trametinib in combination with dexamethasone, cyclophosphamide and cytarabine in children and AYA with R/R ped ALL/LBL whose tumor present with alterations in the RAS-RAF-MAPK pathway.

Key Dates

Start date
Nov 14, 2023
Status verified
Sep 2025
Primary completion
Apr 1, 2029
Completion
Apr 1, 2029

Study Design

Enrollment
26 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Sub-study D
    Trametinib + dexamethasone + cyclophosphamide and cytarabine. Each cycle lasts 28 days. Cycle 1: Trametinib is given orally continuously once a day in tablets or oral formulation depending on the age and weight of the patient. Dexamethasone is given intravenously (IV)/orally on days 1 to 5. Cyclophosphamide is given IV on day 3. Cytarabine is given IV in two blocks of 4 days each one week apart from day 5. Cycle 2 and subsequent cycles: Trametinib is given orally continuously once a day in tablets or oral formulation depending on the age and weight of the patient. Dexamethasone is given intravenously (IV)/orally on days 1 to 5. Cyclophosphamide is given IV on day 1. Cytarabine is given IV in two blocks of 4 days each one week apart from day 3. Patients in dose level -1, receive only 1 block of cytarabine per cycle. All patients receive age adapted intrathecal chemotherapy.

Primary Outcome Measure

Phase I: Maximum tolerated dose (MTD) / Recommended phase 2 dose (RP2D) [ Time Frame: 3 years ]

Central Contacts

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